Preserving the peritoneal membrane in long-term peritoneal dialysis patients.

WHAT IS KNOWN AND OBJECTIVE: Peritoneal dialysis (PD) has been widely used by patients with end-stage renal disease. However, chronic exposure of the peritoneal membrane to bioincompatible PD solutions, and peritonitis and uraemia during long-term dialysis result in peritoneal membrane injury and thereby contribute to membrane changes, ultrafiltration (UF) failure, inadequate dialysis and technical failure. Therefore, preserving the peritoneal membrane is important to maintain the efficacy of PD. This article reviews the current literature on therapeutic agents for preserving the peritoneal membrane. METHODS: A literature search of PubMed was conducted using the search terms peritoneal fibrosis, peritoneal sclerosis, membrane, integrity, preserve, therapy and peritoneal dialysis, but not including peritonitis. Published clinical trials, in vitro studies, experimental trials in animal models, meta-analyses and review articles were identified and reviewed for relevance. RESULTS AND DISCUSSION: We focus on understanding how factors cause peritoneal membrane changes, the characteristics and mechanisms of peritoneal membrane changes in patients undergoing PD and the types of therapeutic agents for peritoneal membrane preservation. There have been many investigations into the preservation of the peritoneal membrane, including PD solution improvement, the inhibition of cytokine and growth factor expression using renin-angiotensin-aldosterone system (RAAS) blockade, glycosaminoglycans (GAGs), L-carnitine and taurine additives. In addition, there are potential future therapeutic agents that are still in experimental investigations. WHAT IS NEW AND CONCLUSION: The efficacy of many of the therapeutic agents is uncertain because there are insufficient good-quality clinical studies. Overall membrane preservation and patient survival remain unproven in using more biocompatible PD solutions. With RAAS blockade, results are still inconclusive, as many of the clinical studies were retrospective. With GAGs, L-carnitine and taurine additives, there is no sufficiently long follow-up clinical study with a large sample size to support its efficacy. Therefore, better quality clinical studies within this area should be performed.

Periostin: a novel tissue biomarker correlates with chronicity index and renal function in lupus nephritis patients.

Lupus nephritis (LN) is one of the most serious complications in patients with systemic lupus erythematosus (SLE). At present, there is no specific biomarker with high sensitivity and renal pathology involvement in use in clinical practice. Periostin is an extracellular matrix protein involved in kidney development and kidney injury. We performed immunohistochemical analysis for periostin and routine staining of 42 kidney tissues from LN patients compared with controlled kidney tissues. Activity index, chronicity index and periostin staining were evaluated and scored by a renal pathologist. Periglomerular staining of periostin was the most predominant finding. Positive periostin staining was also observed in areas with fibrosis such as sclerosed glomeruli, interstitial fibrosis and fibrous vessels. Moreover, the tubules seemed to be the main location for periostin staining. There was a statistically different level of periostin staining score between patient and control tissues. Periostin staining score also correlated with the chronicity index score of renal pathology (r = 0.594, p < 0.001). Periostin was also correlated with worsening renal outcomes including serum creatinine, blood urea nitrogen and estimated glomerular filtration rate (eGFR). Subgroup analysis within patients with low activity index score or low chronicity index score found that there was a statistical difference in serum creatinine and eGFR between groups with low and high periostin staining scores. We concluded that periostin staining score correlated with chronicity index score and renal function in patients with lupus nephritis.

The efficacy of oxymetholone in combination with erythropoietin on hematologic parameters and muscle mass in CAPD patients.

OBJECTIVES: To determine the efficacy of oxymetholone, an androgenic steroid, in combination with rHuEPO on hematologic and muscle mass in CAPD patients. METHODS: A double-blinded, placebo-controlled experimental study was conducted for 6 months and 24 CAPD patients were divided into two groups. The treatment group (n = 11) received rHuEPO plus oral oxymetholone (50 mg/tablet twice daily). The placebo group (n = 13) received rHuEPO plus a placebo twice daily. The evolution of the patients' hematologic parameters and the impact of the drugs on their muscle mass were evaluated. RESULTS: After 6 months of therapy, hematocrit and hemoglobin values of the treatment group were significantly different from those of the placebo group (38.1 ± 1.0% and 32.8 ± 0.9%, p = 0.001; 12.9 ± 0.3 g/dl and 11.0 ± 0.3 g/dl, p = 0.001 for hematocrit and hemoglobin, respectively). The increase in hematocrit and hemoglobin values observed in treatment group was statistically greater than those of the placebo group (p < 0.01). After 6 months, none of anthropometric parameters, albumin, protein or lean body mass levels, were significantly different from baseline in the placebo group. Conversely, most of the anthropometric parameters, albumin and lean body mass levels were significantly increased in the oxymetholone group (p < 0.05). The mean weight of subjects in the oxymetholone group changed from 63.82 ± 2.71 to 67.02 ± 3.26 kg (p = 0.001). The subjective global assessment score for 7 patients in the treatment group (63.6%) changed in a positive manner. A rise in liver enzymes was the main side effect observed in the treatment group. CONCLUSIONS: Oxymetholone significantly enhances the erythropoietic effects of rHuEPO and improves the nutritional status of CAPD patients. However, significant increases in liver enzymes need to be monitored closely.

Oxymetholone ameliorates insulin sensitivity in maintenance hemodialysis patients: a randomized controlled trial.

AIMS: To investigate the beneficial effects of oral oxymetholone on IR in hemodialysis (HD) patients by increasing skeletal muscle function and stimulating myocyte glucose uptake and metabolism. METHODS: In a randomized, controlled double-blind study, 44 patients were randomly assigned to one of two groups: a treatment group that received oxymetholone 50 mg orally twice daily and a control group that received placebo twice daily for 24 weeks. IR was calculated by using HOMA, and dual-energy X-ray absorptiometry was used to determine body composition. All patients were encouraged to walk at least one kilometer daily and were monitored by the Barthel index activity score. RESULTS: 25 men (57%) and 19 women (43%) were studied. 23 subjects were in the control group, and 21 subjects were in the treatment group. The mean age of patients and the duration of dialysis were 43.5 +/- 9.9 years and 92.8 +/- 37.8 months, respectively. After treatment, the HOMA index and body fat mass (FM) were significantly decreased in the treatment group compared to those in the control group (10.8 +/- 16.4 vs. 3.1 +/- 4.5; p < 0.05 and 1.73 +/- 2.77 vs. 0.40 +/- 1.12 kg; p < 0.05, respectively). Concurrently, the mean change of fat free mass (FFM) in the treatment group was higher than that in the control group (3.24 +/- 1.74 vs. 0.65 +/- 1.21 kg, p < 0.05). Two patients in the treatment group experienced an elevation in serum liver enzymes (9.52%). CONCLUSION: HD patients treated with short-term oral oxymetholone showed an increase in insulin sensitivity when compared to the placebo group, and this effect depended on changes in FFM and FM.

Pharmacokinetics of single-dose rosiglitazone in chronic ambulatory peritoneal dialysis patients.

BACKGROUND: End-stage renal disease (ESRD) is associated with marked alterations in the pharmacokinetics of many drugs, not only from reduction in renal clearance but also from changes in metabolic activity, bioavailability, volume of distribution and plasma protein binding. OBJECTIVE: To study the pharmacokinetics of a single 8-mg oral dose of rosiglitazone in patients with ESRD and requiring long-term chronic ambulatory peritoneal dialysis (CAPD). METHOD: The medication was administered just before the first exchange of peritoneal dialysis fluid on the day that blood and peritoneal dialysate collection was performed. RESULTS: In our CAPD patients the mean (+/-SD) T(max) and T(1/2) of rosiglitazone were 1.20 +/- 0.26 and 21.38 +/- 21.96 h respectively. These values were different to those reported for healthy volunteers reported in previous studies. The mean area under the concentration-time curve (AUC((0-infinity))) and an average maximum observed plasma concentration (C(max)) of rosiglitazone in our CAPD patients were 4203.56 +/- 2916.97 ng h/mL and 409.67 +/- 148.89 ng/mL respectively. These appear no different from those reported in healthy volunteers . CONCLUSION: The apparently significant difference in T(1/2) of rosiglitazone in CAPD patients compared with healthy volunteers suggest that dose adjustment may be necessary in order to avoid toxicity.

The effect of serum albumin on the aggregation state and toxicity of amphotericin B.

Studies have shown that the dose-limiting toxicity of amphotericin B (AmB), a key drug for systemic mycoses, depends on its self-aggregation state. In a step toward understanding the various factors in blood mediating the toxicity of AmB, we have investigated the effect of serum albumin, the most abundant plasma protein, on the aggregation state of AmB using absorption spectroscopy. The critical aggregation concentration (CAC) of AmB, which coincides with its concentration at the onset of toxicity (hemolysis), was 1.1 microM, but rose in proportion to the level of serum albumin (1.0 to 4.0% w/v). The CAC of AmB was 8.0 microM at 4.0% w/v serum albumin, which is considerably higher than peak therapeutic levels of AmB in plasma (i.e., 2.0 microM). Serum albumin (4.0% w/v) lowered the degree of aggregation of AmB (size of aggregates) above the CAC and increased its solubility. The results suggest that serum albumin attenuates the toxicity of AmB at a membrane level by affecting its aggregation state. In this way, serum albumin in blood may balance deleterious effects of AmB mediated by serum low-density lipoproteins.